MS Progression: Can It Be Slowed?

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Multiple sclerosis (MS) affects people in a variety of ways and progresses differently in each individual. In this show, you’ll learn about the ways that multiple sclerosis can progress and get expert strategies for slowing it down using drug treatments, alternative therapies and other approaches.

Announcer:
Welcome to this HealthTalk Multiple Sclerosis show. These shows are produced by HealthTalk and supported through an educational grant from MS ActiveSource. We thank MS ActiveSource for their commitment to patient education. MS ActiveSource is sponsored by Biogen Idec and Elan Pharmaceuticals, Inc.

HealthTalk provides resources for people living with multiple sclerosis, but this information is not a substitute for medical care. Please see your doctor for medical advice most appropriate for you.

Our panelists this evening report that they have received funding from the sponsor of the program, Biogen Idec.

The vast majority, about 85 percent of people living with a diagnosis of multiple sclerosis (MS), begin that journey with a relapsing and remitting, or RR, form of MS. A small percentage, however, have a primary-progressive form of multiple sclerosis. In between those two is secondary-progressive multiple sclerosis, the form that everyone that has RRMS hopes they don’t eventually get.

Unfortunately, according to natural history studies, about 50 percent of us diagnosed with RRMS will become secondary-progressive within 10 years. And a very frightening number for us with MS is that 95 percent of us with relapsing-remitting will slip into that progressive phase of the disease within 25 years of diagnosis. I know for myself, as a person living with relapsing-remitting MS that slipped into secondary-progressive, it’s a scary place. Some of the newer studies seem to dispute those numbers, but nobody is disputing that many cases of relapsing-remitting will become progressive forms of this disease.

We’re going to talk about what several of our listeners have asked that we, at HealthTalk, speak of – that progression.

Joining me are two highly qualified panelists. From Washington, D.C., where she is currently an MS specializing neurologist at Georgetown University’s MS Center and soon to be opening the MS Center of Greater Washington, the only free-standing MS center in the D.C. area, is Dr. Heidi Crayton. Dr. Crayton, first off, congratulations on that, and welcome back to the program.

Dr. Heidi J. Crayton:
Thank you so much, Trevis. It’s a pleasure to be here.

Trevis:
Also joining me from the University of Southern California is Dr. Norman Kachuck. Dr. Kachuck is an associate professor of clinical neurology and the director of the MS Comprehensive Care and Research Group. At the head of the Neuroimmunology Division of the department is Dr. Kachuck. Welcome to HealthTalk.

Dr. Norman Kachuck:
It’s my pleasure.

Trevis:Dr. Crayton, the title of our show has to do with the progression of multiple sclerosis. Before we get into that, I’d like for you to define progression as it relates to both MS, the disease clinically and silent disease activity.

Dr. Crayton:I think that everybody would agree that progression means getting worse, by whatever markers that may be. Sometimes patients define progression differently from their physician, but everybody agrees that it means getting worse. Sometimes it means worsening clinically, meaning getting weaker or vision getting worse, and slower gait, more dysfunctional gait. It also means an increased lesion burden that we see on the MRI scan, more spots that are not going away, accumulating over time. Both of those define progression and what progression means.

Sometimes patients can talk about progression in terms of their clinical state. We may not see evidence of that on their MRI scans, but our MRI scans are sometimes insensitive to changes in normal-appearing white matter. Atrophy also plays a role. Sometimes loss of brain tissue or spinal cord tissue is something that we see when people start to progress, get worse. At this point in time, we don’t always have great ways of measuring atrophy.

Trevis:
That’s a scary word for those of us who have MS because we think of atrophy as the muscles deteriorating and withering away, but now you’re talking about brain atrophy. Could you explain that for us?

Dr. Crayton:
Sure. We all experience brain atrophy with aging, but we see it in a more accelerated fashion in people who have MS, especially untreated MS, where we see loss of brain volume, brain tissue or spinal cord. We talk all the time about brain, but this also applies to the spinal cord. And with loss of tissue, circuitry and connections that do a certain job, we lose that particular function. That’s not something that we want to see on the MRI scan.

Trevis:
Last month on our program, I heard the term “breakthrough disease.” Is that the same as progression, this new disease activity is breakthrough disease?

Dr. Crayton:
It’s all about semantics, and what sounds new and different one day is going to be outdated the next. We talk about breakthrough disease as people who are on medicine to try to stabilize their disease progression but who still continue to have progression, decline or continued relapses. They’re breaking through their current treatment.

Trevis:
Thank you, Dr. Crayton.

Dr. Kachuck, since we’re talking about progression, is there anything that can be done to prevent the disease from progressing?

Dr. Kachuck:
I wish I knew. Unfortunately, when you test drugs and therapies for MS, you’re usually limited to a reasonable amount of time to keep people in a clinical trial. That’s a very short time given the number of years that people have the disease diagnosis and are living with it. To the extent that we may have information on two or three years of benefit and, after that clinical trial is over where the drug is shown to be potentially effective, it goes to the FDA, gets approved and gets sold to everybody. Then, we follow some of those folks out for some years. But in the long run, everybody taking therapies now for MS, will they end up with a less progressed disease out 20, 30 years? Nobody really can tell.

To the extent that we can model the disease in animals and are gaining a better understanding of the vulnerability for the disease to cause injury, and the relative ability of that person who has the disease to repair that injury, we’re getting a better understanding of the protection one gets from medicines that might protect from the ongoing process of central nervous system injury during a lifetime.

What we’re talking about are predominantly medicines that we think reduce the inflammation, reduce the chance that immune system activities injure and disable the normal functioning of the nervous system in MS, and to the extent that new promising ways of measuring these medicines take injury process into a quiet mode, and prevent the downstream consequences of that injury.

What we’re not going to be able to tell everybody is whether those downstream injury modulations will not only prevent ongoing immune injury but help in the repair process, and what parts of the central nervous system might exhaust after years of having too much to do in injury and repair.

Trevis:
That was the medical version of a definitive maybe, doctor. Is that what I’m hearing?

Dr. Kachuck:
Darn straight.

Trevis:
Before our audience hangs up or they turn off their computers in frustration, there are definitely things that we can do to live a better life with MS. First, we’re going talk about MS and the symptoms that we just mentioned with Dr. Crayton.

Dr. Crayton, help us understand the difference between MS, the disease and the symptoms of multiple sclerosis.

Dr. Crayton:
We can only really judge the degree of somebody’s disease activity by MRI scans. We do some clinical testing. All of these are what we call surrogate markers. They are what we are using now to get a handle on what’s going on in somebody’s disease process.

We see oftentimes that there’s a mismatch between what’s going on in somebody’s MRI and what’s happening to them clinically or what they’re complaining of in symptoms. People oftentimes say, ‘Well, I have this symptom. Can you show me the correlating spot, the corresponding spot on my MRI scan?” Usually, that’s not possible.

Sometimes we see patients who are getting worse in symptoms, more symptom complaints, but we don’t see much activity on the MRI scan. The flip side of that is sometimes we see people that have very active MRI scans who are quiet clinically. Their exams are unremarkable, and they don’t have too much to say in complaints. The disease itself can certainly be followed by these surrogate markers that we have in MRI and spots, active inflammation and scars that are left, but symptoms people have are something different.

What oftentimes patients are more focused on is quality-of-life symptoms, which sometimes don’t have a corresponding footprint on their MRI scan but get a little bit worse. Things continue or they have spasticity because they have loss of neurocomponents that normally inhibit spasticity. We can’t necessarily see that, but we know that people are experiencing symptoms.

They’re two different concepts that are related but not directly. We can’t point to one and have it correspond to the other.

How’s that for a roundabout answer?

Trevis:
It’s a very good roundabout answer.

So you can’t look at an MRI and see a lesion, a white spot on that MRI, on someone’s brain and say, “Well, that’s what’s causing your bladder issue?”

Dr. Crayton:Correct. You cannot.

Trevis:
The disease itself is what’s causing the demyelination, and the demyelination is thus causing the MS symptom further down the road.

Dr. Crayton:
Correct.

Dr. Kachuck:
Function in the central nervous system has very little to do with specific areas of the brain or spinal cord being injured. It’s a neural networking that recruits different parts of that system in order to get a job done. To the extent that you’ve got noise in the channel that prevents good communication between the various components of that neural network you’ll get dysfunction.

MS makes a lazy neurologist when we have to localize because so many of the ways that MS patients’ nervous systems present with symptoms is well after their brain has started coping and routing the information around areas of injury. A lot of times, we’re not sure what’s going wrong and where. It makes the job of defining the disease that much harder, and we blame MS patients for that entirely.

Trevis:Good, because we blame you, the neurologist.

That’s a very good point because a little later in the program I want to talk about some of the complementary and alternative medicines and exercises, and trying to retrain the brain.

Dr. Kachuck, if these MS platform drugs with which we’re injecting and infusing ourselves aren’t necessarily stopping the progression of the disease MS, what are they doing?

Dr. Kachuck:
Let’s not say that they’re not stopping progression. The best we can say is that the majority of MS patients have a lot of inflammation, especially early in the disease. And that inflammation, by which we mean the immune system getting into the central nervous system and doing something which results in damage, is a process that we can modify using the interferons – the Copaxone (glatiramer acetate), with natalizumab, now marketed as Tysabri, and mitoxantrone and other drugs that are potent anti-inflammatory medicine. To the extent that progression of disease is going to follow inflammation, the degree to which we stop the inflammation is likely to have an ameliorative effect on that ongoing problem in the nervous system.

I’m expecting that given the information we’re getting about what happens to human brain and central nervous systems looking better, with less inflammation, with a reduced number of cell and tissue elements in areas of the brain – to the extent it’s preventing that secondary degenerative component by reducing the bad inflammation, we might be stopping some part of the progressive process.

These are potent medicines that affect the immune system and to some extent might be affecting the way the brain can protect itself from injury and repair itself, given a time out from the immune attack. To the extent that the interferons are helpful in protecting us, I think they will be able to be seen as an anti-progression element. It’s just not going to be the whole story.

Trevis:
That’s good to know. That’s the first time I’ve heard a doctor speak of it that way, and I know that all of our listeners appreciate that, Dr. Kachuck.

Dr. Kachuck:
You’re welcome.

Trevis:
Dr. Crayton, I know that it used to be that a person diagnosed with multiple sclerosis was told to get their affairs in order, quit their job and get ready for a wheelchair. That is not the case today. We’ve got a lot of people who are joining us via the Internet and the phone who are newly diagnosed, and they want to know what their chances are of that kind of progression.

Obviously, acknowledging that no one case of MS is like another, what are our general chances of that kind of progression if we are on a platform therapy?

Dr. Crayton:
You’re right. It used to be the old days were diagnose and adios, a nice pat on the back, and let me know if you have a relapse so I can give you oral steroids. Certainly, things are very different than the old days.

We have natural history data that tells us about half of people that have relapsing-remitting MS will go on to progress within 10 years of their diagnosis, and that increases to about 95 percent within 25 years. That’s natural history data, that’s untreated MS. As Dr. Kachuck mentioned before, we really don’t have definite stats on what degree these disease-modifying agents stave off progression. We are watching people that have been on these medicines, observing them and trying to collect as much data as possible, but at this point in time we can’t say, “Well, if you start a disease-modifying agent at this point you’ll have this percentage reaching this particular EDSS (expanded disability status scale) by this time.”

Trevis:
Doctor, EDSS, make sure that we explain that to our listeners.

Dr. Crayton:
It is the disability scale, which is very heavily weighted toward your ability to walk – the higher the number, the worse the disability. We use that in clinical trials as some objective benchmark or measurement as to how people are doing. So, the higher the number, the more disability.

At this point, we don’t have data to give to people about these medicines when they’re first diagnosed. We don’t have information to be able to say, “Well, starting that medicine today will stave off disability progression in 10 years by this much.” We can say that this particular product decreases physical disability by this percentage, but it’s abstract numbers. I can only imagine if I was being told that I had MS and these numbers were thrown out at me I’d say, “What does this mean for me?”

The upshot is it’s our belief that starting on medicines sooner than later has some positive benefit. It’s not measurable. We haven’t been able to define exactly what that is at this point, but it is our belief that the data certainly supports that we can have an impact on slowing down the disease process. We’re assuming that we’re making some difference in those numbers that you quoted at the beginning of the talk, but at this point it’s very difficult to define them.

People stay doing well much longer than they used to. Of course, people are probably diagnosed much sooner now than they used to be. And that’s key. As Dr. Kachuck said, when people still have compensatory mechanisms in their nervous system to repair, there is still the ability for some restorative mechanisms to make a difference. It’s never too late to be treated, but earlier is better than later.

Trevis:
Dr. Kachuck, we're only dealing in abstracts, but let's talk about those percentages and the way that platform drugs will slow progression. We've all heard numbers of a third and two-thirds as they apply to relapse rate, and that's namely the ABCR platform drugs, the Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (glatiramer acetate injection) and Rebif (interferon beta-1a) They reduce relapse rates by about a third, while Tysabri (natalizumab) purports to do so by two-thirds. Can you help us make sense of these one-third and two-thirds?

Dr. Kachuck:
Yes. But I want to provide a more important segue from what Dr. Crayton said to what your question is now, Trevis. That is, we're doing far more than just delivering drugs to people to change those percentages who go to wheelchair. I think one of the really important things that’s come out of the management of MS research and practice over the last couple or three decades is that there is a lot you can do to control the way this disease progresses by symptom management and a very aggressive physical therapy and rehabilitation program.

We used to be saying rest and get off your feet, and don't do anything when you've got something going on with your MS. That's been proven in MS and other rehabilitation contexts for other diseases as being completely wrong. The reason we're seeing people improve is that we're getting people into reasonably goal-oriented rehabilitation programs and strategies using symptom therapy, identifying psychosocial crises that can be solved, and keeping people functional and optimistic. The degree to which hope works to everyone's advantage, and hope requires feeding with some positive end points reached, has made an enormous difference in the way, at least, I practice medicine now.

Dr. Crayton:
Very true.

Dr. Kachuck:
That's with the caveat that, yes, neurologists can do a certain amount of throwing drugs at people, but they also probably are doing as much or more with a comprehensive management approach to this, we're getting a lot better bang for our buck.

Now, with the issue that you raised about which of these drugs can do better for a particular person given the kind of information you get from a clinical trial, this is an enormous morass. There are a couple of important things that I want to make clear to you folks out there. One is that relapses matter, and certainly you don't want them, and at least 40 percent of relapses result in some sort of disability, but the truth is relapses come and go.

When you are counting relapses, you're counting tips of the iceberg of what's going on with MS. To the extent that you can associate relapses with progression is a problem. It doesn't always connect. As a matter of fact, there are drugs that you can show have a benefit on relapse rate over a certain amount of time that have no effect on progression. There are medicines that have an effect on progression that don't have an effect on relapse rate. There are medicines that have a fantastic result on MRI activity but do squat for people when they're looking at how they feel, their relapses, etc.

We've got enormous disconnects between these various measures that we use to demonstrate efficacy of a drug in clinical trials and how they actually act in real life.

When these medicines are used in trials and you get these results, a result like it drops relapses or progression by a third, means that in a population of people that look about the same the aggregate benefit was this reduction. It doesn't mean that every person had the same drop in that measurable amount. It means that the greatest majority of people who got the benefit of the disease did better than the people who did not get the benefit. There are some people who looked cured on the drug and some people who looked cured on the placebo, but there were fewer of the latter than the former. And the truth is in most of these cases, most people taking both placebo and active treatment look unchanged. It's just that there are more people looking better in the active treatment group and fewer people looking better in the placebo.

You've got to take this kind of outcome with a grain of salt when it is something you're trying to relate to your life. It is absolutely true that a medicine that has a far more robust effect on a given population is probably going to do better for the majority of people than one that is not looking as robust.

When Tysabri was approved, it was approved on the basis of some very robust numbers. The relapse rate was down by 67, 68 percent, progression was down by 40 some-odd percent. The number of disease-free folks, if you judge relapses and MRI events, was profoundly different between the active and placebo groups. All of those numbers reflect much better outcomes in a very large population. This was in a couple of thousand patients. If you're looking over all the trials, that's compared to just a couple of hundred to five, six hundred that were used in the interferon studies.

This was very good news for the MS community that this was going to be a big drug, but it doesn't necessarily mean that everybody is going to look better on it. There are some people who are going to look just fine on the drug they're on, and it's not predictable whether they would look any better on another drug, even though that drug had a more robust finding in population data.

The truth is a good medicine may look good no matter what the population data were for a given person, but you can probably bet that in a certain number of people a drug with a better outcome in one of these trials is going to be better for more people.

Trevis:Those of us who live with the diagnosis of MS know that on some level this is a crapshoot, and it's such a different disease for every person that we're fine with an answer that looks like that. It's nice to hear a doctor that says, “I know but I don't know.” We appreciate that.

Dr. Kachuck:
When we can predict what the responsiveness of a patient is going to be to a medicine, we'll have a much better chance of creating subcategories of MS immunopathologically and in treatment appropriateness. That time is not that far distant. We'll likely be able to decide whether your immune system is going to get a robust response from a drug using lymphocytes, blood cells isolated from you and stimulated in various ways in the laboratory, to see whether we're likely going to get what we need. Then, after a while, take your blood and test it again and see.

That, in complement with other tests, we'll be able to use in order to subdivide this, what we all call MS, into what it probably really is, which is a spectrum of diseases with different immunologic problems and various ways that those immunologic problems should be tackled.

Trevis:Dr. Crayton, most of us with MS are interested in complementary and alternative medicines, also known as CAM. Before we delve into that subject, could you give us some of the examples of these complementary and alternative medicines?

Dr. Crayton:
Sure. Well, the definition is actually twofold, complementary and alternative – complementary meaning used in conjunction with standard of care, and alternative being used in lieu of standard of care. I think patients experience a lot of backlash with the alternative therapies rather than the complementary therapies.

Having said that, complementary and alternative therapies is a huge umbrella that covers nontraditional prescribed medicines. So things like exercise, diet, acupuncture, massage therapy, yoga, tai chi, the use of Chinese medicine or herbs, all those things fall under the umbrella of CAM. Probably close to 75 percent of people with MS use some kind of complementary or alternative therapy for their MS.

This represents about a $15 billion-dollar-a-year industry. But because people are looking for hope and are trying to find something that's going to be the sure thing, it makes people who have MS oftentimes victims of dubious products and claims, claims that allege to help people with MS but have not been shown to be effective at all.

A lot of these things can be very costly, and the bottom line is if it sounds too good to be true, it probably is. There's so much brainwashing out there and pulling people into some of these more dubious complementary or alternative therapies that are very costly and end up having more of a negative impact.

Back to the positive side of CAM, I think that there's certainly a role for those things that I listed. It's important when we're talking about herbs with patients. I want them to tell me the various herbs that they're taking because there are some things that claim to boost the immune system that we don't want people with MS to be taking. Things like echinacea are proposing to be immune enhancers. People with MS already have a very enhanced immune system, so we want to stay away from those things.

I certainly think there is a role for complementary and alternative therapies in many cases because they treat some of the symptoms and subjective and intangible aspects of MS, which we in Western medicine are not very good at identifying, pinpointing and treating. There is room for a lot of those therapies to decrease those somatic things which impact – whether or not we can quantify it – somebody's experience with MS.

Trevis:
I know that as part of the service that we provide here at HealthTalk is an ever-expanding blogosphere. Something that I read just recently was that conspiracy theory that doctors and drug companies don't want to find a cure for MS. But I think all in the medical field would go on the record that that is just conspiracy theory and bunk, is that correct?

Dr. Crayton:
Correct.

Trevis:
Dr. Kachuck, it's been said that, ”A cure for MS is different things to many people.” There are three cures people speak of. One is to stop the progression of MS, two, repairing the damaged myelin that already exists. Three would be a vaccine that keeps people from getting MS in the first place. Which of those three “cures” do you think we are closest to right now?

Dr. Kachuck:It's an exciting question, and everybody needs to keep the word "cure" somewhere up on the list of priorities for us to – when we wake up every morning as MS clinicians and researchers and patients or people living with MS – aim at, not just these halfway measures of controlling this or controlling that.

The cure of this disease is problematic because I don't think it's a single disease. There are some kinds of MS that are going to be far more likely to see a “cure” than others. The person with a very active inflammatory disease mediated by a very small number of types of immune cells that can be deleted out are probably going to get what you'd imagine to be called a cure using vaccination in the not-too-distant future. That's to say that – not like a vaccine where you would have someone never having had MS and thus never diagnosed given a vaccine to prevent, but – a vaccination that once a person is identified as having MS they could receive and then see the diminution and removal of the offending element. That is probably the closest cure that we're going to see for some people.

Repairing damage – and let's be clear that we're not just talking about myelin – disability accrues because not just the myelin is being affected but axons, the actual nerve track that is being damaged are being affected by it. We need to fix those too. And you already do fix yourself. How do we enhance that? I think that the final common pathway of cell injury in MS is the same as it is in Alzheimer's and Parkinson's and every other disease that affects the central nervous system causing cell damage. That means there are a lot of people working on that problem from a lot of different angles. I would bet that we will see a significant number of new ways of helping damaged central nervous system repair in the not-too-distant future. I would put that second.

The progression of MS is going to be something that is very hard to measure. In terms of a cure, I don't think that is what we'll know we are doing in a majority of patients. We'll see short-term and, perhaps, partial cures because of effects on measures of progression in several different kinds of MS, including the folks who have secondary-progressive and still have inflammatory disease.

Trevis:
Dr. Crayton, talk a little bit about the concept of genetic therapy and MS, if you would.

Dr. Crayton:
That's probably more a Dr. Kachuck topic than mine. I wouldn't fancy myself the geneticist or the genetic researcher by any means.

I think that this is a very exciting time for MS and MS therapies because there is so much going on in MS therapy. The disease is being approached from all angles, which is very exciting as a MS-ologist. But people want to know when the cure is going to happen. I think it's more exciting that we're approaching MS from a genetic point of view, an immunological point of view and a clinical point of view trying to slow down disability and looking at MS as a whole spectrum and not an isolated disease state.

We're moving away from looking at people, pigeonholing them as relapsing-remitting, secondary-progressive or primary-progressive to fit into these little boxes, and starting to view MS as this spectrum of disease. And there are components of those types of MS which allow us to approach disease modification and cure from many different approaches. That's the exciting part.

I can't talk too much about genetic therapies and generic research, but I can tell you that I think it's very exciting that we're approaching it.

Dr. Kachuck:
When you're talking about gene therapy, you have two different things you're talking about. One is you're changing genes in a body, which is practically impossible, and we probably won't be doing much of that. But if you want to introduce genes in order to make a gene product that will change the system, I think that is something that we're going to see a lot of. The basis of that is that there's a vulnerability to injury and an inability to repair, two sides of the problems that MS people have. As such, there are very different pathways that you can affect that, one, will modify that injury susceptibility and, two, will affect some of the repair process.

USC, where I practice, is engaged in a very aggressive approach to identifying the genetic vulnerabilities to injury and repair that are present in MS. The ways we have of using modern technology to assay the human genome for differences in the MS population compared to the general population is going to be bearing fruit as we speak. It will aim researchers at ways that those genes and their mutations will be amenable to treatment.

The undercurrent of what we should say about gene therapy, the real take-home, is that we are understanding far more about how multiple gene vulnerabilities end up causing disease. The things that those genes make could potentially be supplemented or altered by therapies that are introduced into the body, perhaps introduced as genes that can be programmed to produce the desired gene product.

Trevis:
Thank you very much, doctor. We are going to get on to questions. Our first question is from Claire in Ontario, Canada, to talk about exercise. Claire, you're on HealthTalk.

Claire:
My question is, is there any exercise that's better in helping MS patients to cope with the progression of their disease?

Dr. Crayton:
I don't think that there's any particular exercise that is better than another type. It's important to do what you're able to do and what's safe for you to do. Stretching is always a very important part of any exercise program when you have MS because oftentimes spasticity plays a role in disability, not just weak muscles.

I tout the benefits of yoga to my patients. You get a lot of bang for your buck. You have improvement in muscle strength, muscle tone and balance.

Doing anything in the water is great. If you have difficulty walking, if you have a floatation device around your waist and walk in the shallow end of the pool, short laps back and forth, you have the resistance of the water, but you're more buoyant, and you're able to stay cool.

Things like that that can be productive in getting exercise. But you don't want to push yourself beyond the limits of comfort, where you have to recover from an exercise program. Something that incorporates strengthening, flexibility and balance is the way to go, for everybody.

Trevis:
Thank you, doctor. Claire, my physiatrist, says that stretching is something everyone should do. So your care partner that's there, anyone listening in support groups, all of you should be stretching every day.

We've got a question from Dale in Fort Collins, Colorado. "What is your opinion on the Tysabri (natalizumab) treatment, and do you see a beneficial long-term effect that's over the 24 months that's been studied?"

Dr. Kachuck:
The Tysabri benefits were the same at one and two years in the pivotal trials published. The effects were maintained. In the long-term benefit of Tysabri on MS, only time will tell.

One of the wonderful outcomes of the whole debacle that was Tysabri and this viral infection from JC virus, PML (progressive multifocal leukoencephalopathy), is that when Tysabri came back on the market it came with suggestions about how to follow patients, who are on a new medicine as part of the official rollout of that medicine in a registry, so that we can keep track of what's going on far out from the original time of introduction. We can start looking at exactly what we were talking about at the beginning, which is what happens to people on these drugs for a long time.

One of the big blessings of Tysabri will be that the FDA is going to now mandate that nearly all drugs coming on market are in a modified registry. Tysabri will lead the pack, and we’ll probably have very good ascertainment of all the people taking Tysabri, meaning we'll capture nearly everybody who's taking it in a database that looks at how they do. I'm very hopeful. I think it's going to be a wonderful robust therapy for MS.

Trevis:
Susan is sending an e-mail to Dr. Crayton, "Does progression of MS include depression?"

Dr. Crayton:
Depression is a symptom of MS. Depression can certainly get worse. It can progress as a symptom, and that may or may not correlate with an increased number of spots that are seen on the MRI. But depression is a very common symptom that we see with MS. It's not rare. It's something that we see with many people that have MS. It's a symptom that needs to be treated as aggressively as bladder dysfunction, spasticity or visual disturbance. We need to treat it as something that's just as important and not something that is a sidebar issue.

Trevis:
Our next question is being e-mailed in from Tammy in Lubbock, Texas. "With secondary-progressive MS, how can one tell when the worsening is occurring because it seems to be so subtle?" Dr. Kachuck?

Dr. Kachuck:
Tammy, you can't know. One of the problems that people have with hypertension (high blood pressure) is that it's a silent killer. You don't often know when your blood pressure is up. You don't know when the medicine is working for you when you're taking your MS injectables every day, every other day, every week. You can't be sure that it's doing what it's supposed to be doing.

The truth is that the doctor's exam and your exam, by virtue of how you keep track of what you can and can't do, reflect over time any changes that have occurred. Try to see any trends that are out of proportion to what you expect and report those to your healthcare provider. Then, aggressively do something about it. That's the best way that we can handle this.

Trevis:
Tammy, I have to tell you as a person living with secondary-progressive MS, a health log or diary helps. I do an inventory every morning of what I can feel, what I can't feel, what moves and what moves the same way as it did the day before. Keeping track of your symptoms for yourself helps. Also, if you have someone who is in your life on a daily basis, having them be part of that and keeping a journal for themselves, that helps a lot. Hopefully, those will help you quite a bit.

Dr. Kachuck:There is a certain amount of obsessive-compulsiveness that you can get into if you're trying to measure things too carefully too often. You can get very much invested in small changes. You’ve got to watch trends. Trends are bigger than day-to-day, but the day-to-day data are important. Don't fuss over the little stuff.

Trevis:
That's why the concept of having that journal, so that you can read through it before your biannual exam, gives you the chance to look over what is a trend and what might be a spike.

Dr. Kachuck:
Right.

Trevis:
Next, we have a question that's coming in via e-mail from Salem, Wisconsin. "I swim every other day. It helps me a lot, but does it really help my progression?" Dr. Crayton?

Dr. Crayton:
I wouldn't say that it has an impact on what the MRI looks like, whether or not there is change in the MRI scan. But progression has so much to do with keeping your body well and keeping yourself from being disabled by keeping your body functional. Those are just as important elements. By swimming every other day and doing what you're doing, are you staving off progression? Probably not, in terms of the disease, but are you staving off disability? Yes. Those are oftentimes two different concepts. So it's not for naught. It is a very important part of staving off disability. Keep it up because you're doing a great job by doing it.

Trevis:
I'd like to throw in there a healthy body will stay healthy, and it will recover better.

Dr. Crayton:
Recover better, that's right.

Dr. Kachuck:
There is very good evidence from investigations of stroke patients and brain injury patients using functional MRI and rehabilitation measures that if you exercise the part of the body attached to the brain that's been affected by neurologic insult, it does much better than if you let it go and not concentrate on it. It makes every difference in the world to actively challenge the body and the body-mind connection, through the brain, to attain reasonable goals in return of function.

I think you can stave off progression if you are exercising. You can train this mass of jelly up there to do stuff that you need to do even when you don't have MS. God knows this neurologist has to do a lot to keep himself in shape, and he does it by doing exactly what you're doing. We all don't have any choice.

Trevis:
We have a caller on the line. Elaine is calling from Pennsylvania. Elaine, you are on HealthTalk.

Elaine:
I've just been newly diagnosed, and sometimes my legs work well, and then in a couple of weeks they don't. But then they seem to go back to where they were. Does this mean that that's progressive? Or is that common?

Dr. Crayton:
No, that's actually very common. That does not necessarily mean that there is progression going on, especially, like you said, if you bounce back to where you had been. People have ups and downs. That's the nature of the beast. People have good times and bad times. People who talk about progression talk about this steady change, steady decline. But it sounds like you have periods of time when things are worse, but then they get better. That is very common with many symptoms, not just leg weakness or walking problems. Sometimes people say that about their vision.

Sometimes people see changes like that occur when their bodies overheat, when they are in very stressful situations, and when they have an infection, for instance. So that's a very common thing that can happen in relapsing and remitting MS. You have good times and bad times, and your body bounces back.

Trevis:
I have to congratulate the caller and for all of you who are newly diagnosed for tuning in to HealthTalk and getting all the information that you can as soon as possible. We all know that with MS, as with many other things, knowledge is power.

I have a question that's just been e-mailed in to us from Susan from Staten Island, New York. "Is it time to change medications when you start to have progression with this disease? For instance, I've been on a therapy for three years, and I've started to notice it's (my MS) getting worse. Is it time to change, or should I stay the course? Dr. Kachuck, what's your opinion?

Dr. Kachuck:
In general, you've got to make sure that you've optimized everything else that you're doing with your body and the symptoms before you know that this is an effect or a lack of effect from your disease-modifying agent. It certainly isn't good to get worse. And to the extent that you may have to change your disease-modifying agent after you control for all these other factors, it may be important to look at it as a failure of the immune modification.

A lot of times people fail because they've fallen off the wagon of their lifestyle enhancements. There are other things going on. As you live with a chronic disease, as one caller pointed out, depression happens. Depression is going to be a big deal, and your mood and your approach to this disease is going to be as much a factor of how you function as anything else.

So with that said, you control for all those various things that you can change short-term with your lifestyle, to various symptomatic therapies, and then you and your doctor decide whether you're going to reasonably change. Three years is a good time. I know that the average switch at this point is still somewhere around a year, which means that everyone is giving up a little too fast. These disease-modifying agents probably don't work for at least some months before they start changing things immunologically, radiologically.

Tysabri had this wonderful kickoff, so that within six weeks or so you can see big differences. But for the most part a person who's out three years, you've exhausted everything else, you've tried even some pulse corticosteroids added to your platform therapy; it's probably time to change. What you're going to change to is a topic which will take us far beyond the time we have planned for this conversation.

Trevis:
Speaking of time, we're running very short. So, Dr. Crayton, I'm going to give you a question, and you've got about 30 seconds to answer.

It's an e-mail from Kate in Raleigh, North Carolina. It says, "I've heard about many oral drugs being studied in clinical trials. Are there any that are close to being approved? And if so, what are your thoughts on the concept of oral drugs?"

Dr. Crayton:
There are two that are on the horizon. FTY720, which is also called fingolimod in the study [Novartis Pharmaceuticals], and BG-00012 [Biogen Idec]. These are the two oral agents that are forthcoming in clinical trials. For the former, the clinical trial is already enrolling, and for the latter, is soon to be enrolling.

We want MS trials to take two years, and then we collect data, put it all together and present it to the FDA. These products, if they are shown to be effective, are not going to make it to the marketplace for at least two, three years.

Trevis:
I'd like to thank both our doctor panelists and all of you who submitted your questions. We appreciate your time and your attention. From all of us at the HealthTalk studios in Seattle, Washington, and the HealthTalk MS Education Network, I'm Trevis Gleason. We wish you and your families the best of health. Cheers.

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